Genetic Core

说明）： 核心C将为所有核心和项目1提供生物库、遗传分析和信息学服务 和2.核心C将保存和分发样本、细胞系和基因构建体。核心C也将评估 家族性和非典型帕金森综合征的遗传贡献，重点是相关的致病突变， 相关的易感性变体。有四个具体目标： 目标1）信息学：提供、维护和改进核心B、C之间的数据存储和集成 和D，以及项目1、2和3。最低限度的临床、病理和谱系数据包括主要 诊断、谱系关系和样本可用性。基因型数据将随附于样本中 标识符。核心C将提供变异选择、描述性统计和把握度分析方面的帮助， 帮助管理样本和系谱确定。 目标2）生物库：个体样本包括条形码化的血液、细胞系和脑组织， 信息追踪。DNA将从血液或冷冻脑中分离，生物标本将是高质量的。 控制和存档。储存库包括克隆基因的细胞系和质粒，连接或 与帕金森综合征相关，作为阳性对照，可根据要求分发。 目的3）评估与帕金森症相关的基因中的罕见和常见变异：完整基因 将根据多发病帕金森病家族的疾病遗传模式进行测序， SNCA、LRRK2、EIF4G1。VPS 35、PRKN、PINK 1和DJ-1。所有点突变和定量外显子 还将检查与单基因形式的帕金森综合征相关的缺失/重复突变。此外，本发明还提供了一种方法， 我们的筛查将包括对常见的既定遗传风险因素的评估。 目标4）为马约尤德尔中心和外部项目提供核心基因分型设施 Udall网络：项目1和项目2需要对特定基因和变体进行基因分型。核心 C将根据项目3的需要提供额外的动物模型基因分型。Core C还将支持和 促进Udall中心之间建立和新的合作，并根据要求提供遗传分析。 相关性（参见说明）： 帕金森氏症的遗传学发现已经彻底改变了体外和体内研究领域 疾病模型系统和产生治疗开发的新途径。核心C将 根据需要为所有核心和项目提供生物库、基因分型和信息学服务， 此外，促进与其他尤德尔中心的遗传组成部分的合作。

instmctions): Core C will provide biobanking, genetic analysis and informatics services for all Cores and for Projects 1 and 2. Core C will maintain and distribute samples, cell lines and gene constructs. Core C will also assess the genetic contribution to familial and atypical parkinsonism, focusing on linked pathogenic mutations and associated susceptibility variants. There are four specific aims: Aim 1) Informatics: To provide, maintain and improve data storage and integration among Cores B, C and D, and for Projects 1, 2 and 3. Minimal clinical, pathological and genealogical data includes major diagnoses, pedigree relationships and sample availability. Genotype data will be appended to sample identifiers. Core C will provide assistance with variant selection, descriptive statistics and power analyses to help manage sample and pedigree ascertainment. Aim 2) Biobanking: Individual samples include blood, cell lines and brain tissue that are bar-coded and informatically tracked. DNA will be isolated from blood or frozen brain, and biospecimens will be quality controlled and archived. The repository includes cell lines and plasmids of cloned genes, linked or associated with parkinsonism, that serve as positive controls that may be distributed on request. Aim 3) Assessment of rare and common variants in genes linked to parkinsonism: Complete gene sequencing will be performed based on disease inheritance pattern in multi-incident Parkinsonian families for SNCA, LRRK2, EIF4G1. VPS35, PRKN, PINK1 and DJ-1. All point mutations and quantitative exonic deletion/duplication mutations linked to monogenic forms of parkinsonism will also be examined. In addition, assessment of common established genetic risk factors will be included within our screens. Aim 4) Provide core genotyping facilities to the projects of the Mayo Udall center and external Udall network: Genotyping of specific genes and variants will be required for Project 1 and Project 2. Core C will provide additional animal model genotyping as needed for Project 3. Core C will also support and foster established and new collaborations between Udall Centers and provide genetic analysis as requested. RELEVANCE (See instructions): Genetic discoveries in parkinsonism have revolutionized the research field directing in vitro and in vivo disease model systems and generating novel avenues of therapeutic development. To this aim Core C will provide biobanking, genotyping and infonnatics services for all Cores and Projects as required and additionally foster collaborations with the genetic component of other Udall Centers.